Structural influences on the activity of bismuth(III) indole-carboxylato complexes towards Helicobacter pylori and Leishmania

Seven new bismuth(III) complexes derived from indole-carboxylic acids have been synthesised: five are homoleptic; [Bi(IAA)(3)] B1, [Bi(IPA)(3)] B2, [Bi(IBA)(3)] B3, [Bi(MICA)(3)] B4, [Bi(IGA)(3)] B6, and two are heteroleptic [BiPh(MICA)(2)] B5 (where IAA-H=2-(1H-indol-3-yl)acetic acid, IPA-H=3-(1H-indol-3-yl)propanoic acid, IBA-H=4-(1H-indol-3-yl)butanoic acid, IGA-H=2-(1H-indol-3-yl)-2-oxoacetic acid, and MICA-H=1-methyl-1H-indole-3-carboxylic acid). All complexes were fully characterised by elemental analysis, infrared and mass-spectroscopy, and nuclear magnetic resonance (H-1, C-13) spectroscopy. Complex [BiPh(IGA)(2)] B7 is structurally authenticated by X-ray crystallography as a dimer in the solid-state. The in-vitro anti-bacterial activity of the indole-carboxylic acids and their bismuth(III) complexes was assessed against Helicobacter pylori. While the acids were non-toxic at <100 mu gmL(-1), all the bismuth compounds showed an MIC of 6.25 mu gmL(-1), indicating that the anti-bacterial activity is insensitive to the degree of substitution at the Bi(III) centre or the composition of the indole-carboxylate ligands. All compounds were further tested for their anti-parasitic activity against Leishmania major and for their toxicity towards mammalian cells. From the anti-parasitic studies, it was found that the heteroleptic bismuth(III) complexes are the most active, with B5 and B7 showing comparable activity to Amphotericin B, without any toxicity towards the mammalian cells at their effective concentration.